Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1

Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 mill...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Scientific reports Ročník 6; číslo 1; s. 33887
Hlavní autoři: Yan, Naihong, Cheng, Lin, Cho, Kinsang, Malik, Muhammad Taimur A., Xiao, Lirong, Guo, Chenying, Yu, Honghua, Zhu, Ruilin, Rao, Rajesh C., Chen, Dong Feng
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 28.09.2016
Nature Publishing Group
Témata:
14/63
38/15
38/61
45/29
631/80/304
64/60
692/699/3161/3175
Degenerative diseases
Derepression
Embryogenesis
Embryonic growth stage
Fetuses
Gene deletion
Histone methyltransferase
Homeostasis
Humanities and Social Sciences
multidisciplinary
Photoreceptors
Retina
Retinal degeneration
Science
Science (multidisciplinary)
ISSN:2045-2322, 2045-2322
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:Some adult-onset disorders may be linked to dysregulated embryonic development, yet the mechanisms underlying this association remain poorly understood. Congenital retinal degenerative diseases are blinding disorders characterized by postnatal degeneration of photoreceptors, and affect nearly 2 million individuals worldwide, but ∼50% do not have a known mutation, implicating contributions of epigenetic factors. We found that embryonic deletion of the histone methyltransferase (HMT) Ezh2 from all retinal progenitors resulted in progressive photoreceptor degeneration throughout postnatal life, via derepression of fetal expression of Six1 and its targets. Forced expression of Six1 in the postnatal retina was sufficient to induce photoreceptor degeneration. Ezh2 , although enriched in the embryonic retina, was not present in the mature retina; these data reveal an Ezh2 -mediated feed-forward pathway that is required for maintaining photoreceptor homeostasis in the adult and suggest novel targets for retinal degeneration therapy.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2045-2322
2045-2322
DOI:10.1038/srep33887